Daniel Kuritzkes, M.D., is the director of AIDS Research at Brigham and Women's Hospital in Boston, Mass., and an associate professor of medicine at Harvard Medical School. He presented a study at CROI 2007 examining the effects of NNRTI resistance on drug regimens containing efavirenz (EFV, Sustiva, Stocrin). In this interview, he talks with The Body Editorial Director Bonnie Goldman about the study's findings.

What we found [in this study] is that anybody who had efavirenz resistance detectable by standard genotyping and received a three-drug regimen of zidovudine [AZT, Retrovir], 3TC [lamivudine, Epivir] and efavirenz failed on their efavirenz regimen. Overall, they were three times more likely to fail than people who did not have resistance, and the average time to failure was a little bit more than 24 weeks.

The patients who received a four-drug regimen of zidovudine, 3TC, abacavir [ABC, Ziagen] and efavirenz actually had similar rates of failure. They had similar prevalence of resistance, in the failure and non-failure groups, but they were small numbers. [Therefore,] it's hard to say what the impact of the fourth drug was.

I think the implication of this study is that we should be screening patients ... by doing resistance testing before choosing a first-line regimen. I think it's also possible that more sensitive tests, like allele-specific PCR [polymerase chain reaction], could detect still more patients with resistance, and work is underway [on that].

Have there been a lot of studies proving that patients had NNRTI resistance when they first came in to the clinics?

No. This is one of the first controlled studies that really looked at this. People have seen baseline resistance, and they've noted failure in patients who have baseline resistance. It's never been done with a suitable control group to, first of all, exclude the occurrence of baseline resistance in successfully treated patients, and also ... compare the rates of resistance.

Why do you think resistance to NNRTIs is so common, as opposed to NRTIs?

I think that NNRTI resistance has become more common because it persists after stopping a drug, and is readily transmitted without a significant fitness cost to the virus. I think it's now the most common ... form of resistance in patients failing first-line regimens. It just reflects the common use of NNRTI-based regimens.

I believe that the parent study for this trial showed a racial difference, as well. Also, I think [the parent study found that] NNRTI resistance was more common in MSM [men who have sex with men] than in, let's say, African Americans or poorer patients.

The parent study on which this trial is based showed that blacks were more likely to fail because of different patterns of non-adherence, so that adherent blacks and adherent whites had the same success rate. Non-adherent blacks were more likely to fail than non-adherent whites, which would argue that the pattern of non-adherence was different by ethnic group. We didn't see a difference in distribution of resistance by ethnic group in our study.

What percentages of females and males were involved?

In the study overall, 18% were women. In the sub-cohort, it was about 85% men, so 15% women. This was a random subset of the entire study. There were more NNRTI-resistant men [than women] -- 92% of the NNRTI-resistant patients were men.

Is that because they exist in a world where NNRTI treatment regimens are more common?

That's certainly possible. There may be more MSMs, who have been exposed to NNRTIs, who are transmitting resistance to other MSMs, than there are men transmitting to women or women transmitting to male partners.

Is this study over or is it ongoing?

[T]his study is completed. The primary manuscript from this study was published this summer in JAMA [Journal of the American Medical Association] -- the comparison of the three- and four-drug arms. This is one of the secondary analyses that we have been doing.

This article was provided by TheBodyPRO.com. It is a part of the publication Exclusive Coverage of the 14th Conference on Retroviruses and Opportunistic Infections.

Please note: Knowledge about HIV changes rapidly. Note the date of this summary's publication, and before treating patients or employing any therapies described in these materials, verify all information independently. If you are a patient, please consult a doctor or other medical professional before acting on any of the information presented in this summary. For a complete listing of our most recent conference coverage, click here.

TheBodyPRO.com is a service of Remedy Health Media, LLC, 750 3rd Avenue, 6th Floor, New York, NY 10017. TheBodyPRO.com and its logos are trademarks of Remedy Health Media, LLC, and its subsidiaries, which owns the copyright of TheBodyPRO.com's homepage, topic pages, page designs and HTML code. General Disclaimer: TheBodyPRO.com is designed for educational purposes only and is not engaged in rendering medical advice or professional services. The information provided through TheBodyPRO.com should not be used for diagnosing or treating a health problem or a disease. It is not a substitute for professional care. If you have or suspect you may have a health problem, consult your health care provider.